TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7560	22903;22904;22905	chr2:178721985;178721984;178721983	chr2:179586712;179586711;179586710
N2AB	7243	21952;21953;21954	chr2:178721985;178721984;178721983	chr2:179586712;179586711;179586710
N2A	6316	19171;19172;19173	chr2:178721985;178721984;178721983	chr2:179586712;179586711;179586710
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-60
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.2606
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
N/D	None	None	0.943	N	0.403	0.218	0.173771789658	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85941E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
N/A	0.5472	ambiguous	0.6288	pathogenic	-0.803	Destabilizing	0.593	D	0.432	neutral	None	None	None	None	N
N/C	0.6883	likely_pathogenic	0.7466	pathogenic	0.108	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
N/D	0.5236	ambiguous	0.5581	ambiguous	0.372	Stabilizing	0.943	D	0.403	neutral	N	0.411148188	None	None	N
N/E	0.8592	likely_pathogenic	0.9007	pathogenic	0.42	Stabilizing	0.986	D	0.366	neutral	None	None	None	None	N
N/F	0.8086	likely_pathogenic	0.8404	pathogenic	-0.78	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
N/G	0.6055	likely_pathogenic	0.6788	pathogenic	-1.075	Destabilizing	0.995	D	0.369	neutral	None	None	None	None	N
N/H	0.2497	likely_benign	0.3078	benign	-0.731	Destabilizing	0.999	D	0.449	neutral	N	0.421826541	None	None	N
N/I	0.4558	ambiguous	0.5125	ambiguous	-0.137	Destabilizing	0.996	D	0.586	neutral	N	0.456285832	None	None	N
N/K	0.6288	likely_pathogenic	0.7399	pathogenic	0.081	Stabilizing	0.732	D	0.229	neutral	N	0.392636998	None	None	N
N/L	0.4596	ambiguous	0.5327	ambiguous	-0.137	Destabilizing	0.99	D	0.52	neutral	None	None	None	None	N
N/M	0.6219	likely_pathogenic	0.6848	pathogenic	0.188	Stabilizing	1.0	D	0.559	neutral	None	None	None	None	N
N/P	0.7631	likely_pathogenic	0.8004	pathogenic	-0.33	Destabilizing	0.998	D	0.52	neutral	None	None	None	None	N
N/Q	0.6474	likely_pathogenic	0.75	pathogenic	-0.439	Destabilizing	0.997	D	0.419	neutral	None	None	None	None	N
N/R	0.6659	likely_pathogenic	0.7609	pathogenic	0.114	Stabilizing	0.993	D	0.417	neutral	None	None	None	None	N
N/S	0.1557	likely_benign	0.183	benign	-0.521	Destabilizing	0.393	N	0.225	neutral	N	0.424077413	None	None	N
N/T	0.3358	likely_benign	0.4	ambiguous	-0.28	Destabilizing	0.254	N	0.219	neutral	N	0.435833202	None	None	N
N/V	0.5151	ambiguous	0.5992	pathogenic	-0.33	Destabilizing	0.967	D	0.527	neutral	None	None	None	None	N
N/W	0.9331	likely_pathogenic	0.9487	pathogenic	-0.549	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/Y	0.3539	ambiguous	0.3966	ambiguous	-0.347	Destabilizing	1.0	D	0.557	neutral	N	0.446588913	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.